D1.324 - JAK Inhibitors in the Treatment of Chronic Mucocutaneous Candidiasis in a Patient with STAT1 Gain-of-Function Mutation

A 16-year-old Iranian girl born to consanguineous parents with a healthy younger brother presented with a history of chronic mucocutaneous candidiasis (CMC), autoimmune hepatitis, and poor specific antibody responses to vaccinations. Whole-exome sequencing (WES), performed in August 2010, identified a heterozygous gain-of-function mutation in the STAT1 gene, which was confirmed by Sanger sequencing. Her parents and brother have homozygous wild-type alleles.

The patient's oral thrush started at 17 days of age and had a history of recurrent nail candidiasis and respiratory tract infections since infancy. At 16 months of age, she was admitted to the hospital with oral candidiasis, cough, and respiratory distress. Laboratory tests revealed leukocytosis (WBC 16,300/mm³), anemia (Hb 10 g/dL), and elevated IgM (51 mg/dL). She was treated with ceftriaxone, clindamycin, and nystatin.

When she was 6 years old, she was hospitalized with fever, scleral icterus, right upper quadrant abdominal pain, hepatomegaly and elevated liver enzymes, positive ANA and anti-LKM antibodies. Laboratory assay ruled out Wilson’s disease, viral hepatitis, and lysosomal storage disorders. Liver biopsy revealed moderate chronic hepatitis with mild fibrosis, consistent with an autoimmune aetiology. The laboratory findings included leukopenia, with the CD19 level : 3%, CD21 level: 0.5%, undetectable IgA, and low IgG (557 mg/dL). Her specific antibody titers to tetanus and diphtheria were <0.03 IU/mL, and she was started on monthly intravenous immunoglobulin (IVIG). Fungal studies identified dermatophytes in the skin and nails, and oral swabs repeatedly revealed the Candida albicans complex. She received prednisolone and ursodeoxycholic acid. Recurrent pneumonia, oral and cutaneous aphthous lesions, generalized edema, and clubbing had been observed. At the age of 8, she presented with a massive pericardial effusion requiring pericardial drainage. Bronchoalveolar lavage and biopsies were negative for CMV, HSV, and TB. Despite multiple antifungal regimens, she experienced frequent relapses. At age 10, she was started on sirolimus and corticosteroids, with some clinical benefit. She received caspofungin and voriconazole, followed by the initiation of baricitinib (4 mg daily). With the continuation of baricitinib for one year, her fungal infection episodes and hospitalisation were controlled.